ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

This will be my last blog at this Conference. I have been very privileged to have been able to attend CROI this year, my very first time (one of 25% of the first time delegates, I am told).

As the late Joop Lange had said, "Continue to do good Science"

It has been wonderful to meet up with my fellow "blogger" colleagues - Levinia Crookes, Julian Langton-Lockton, Jane Hunt, Marilyn McMurchie. We have certainly shared our experiences with one another.

There may be a few 'blogs' on this topic of PEP, but I will add my own perspective on this themed discussion.

Kenneth Meyer from Fenway Health, Boston was the Discussion leader. He talked about the challenges of PEP research (including the fact that guidelines are based on review of case series) and reminded us about the 2014 WHO guidelines on PEP to prevent HIV infections in adults, adolescents and children.

- The study suggested there is lack of clinical guidance in the clinical management of Acute HIV in the setting of PEP and that in the setting of acute HIV diagnosis after PEP initiation , recommendation to continue PEP until urgent review by HIV specialist where pros and cons of continuing vs stopping ART can be discussed

The Webcasts will be available soon and I would encourage colleagues to look at them.

The 4 speakers were from Spain, Australia, Thailand and the UK.

It was interesting to be aware of what is being used for PEP in each of the countries.

The speaker from Barcelona mentioned that they used Truvada and Raltegravir.

In Bangkok, Nevaripine and Kaletra are used.

In the UK, various regimes are used including Truvada and Raltegravir, Truvada and Kaletra.

In Australia, again, various regimes are used - 2 drug to 3 drug regimes depending on the risk according to our guidelines, as we already know. (I did not know this until today but one regime used in 1 centre is 3TC/TDF/d4T)

Several suggestions included:

1) That the full course of PEP should be given at first presentation rather than just the starter pack - ? to increase compliance.

2) 3 drugs should be used.

The issue of cost remains a consideration.

If already infected (very early infection) when initiating PEP, the question of what happens with very early treatment in this scenario remains.

Statin effects on arterial inflammation could not be adequately assessed but atorvastatin reduced a systemic marker of vascular inflammation

2. There appears to be a potential association of choline metabolism to subclinical atherosclerosis in HIV, assessed in relationship to plaque burden with the use of a sensitive CG angiographic technique

This relationship may be from altered gut flora or microbial translocation unique to HIV.

There is a need to assess the role of gut micro biome on CVD in HIV

3.The study on varenicline would be of interest to primary care physicians. Varenicline is safe and well-tolerated and effective as an adjunct to counselling in HIV positive patients as in general population and should be considered in HIV case management

Treatment of tobacco dependance in PLWH is a challenging priority.

4. PI/r or INSTI regimen initiation led to similar increases in limb fat with similar increases in central fat but ATV/r containing arm tended to have higher gains in Lean Body Mass (LBM) than DRV/r but LBM gains were similar in pooled PIs vs INSTI

Higher pre-ART inflammatory markers were associated with increases in peripheral fat and LBM but not central fat

5. Studies have shown an association between the use of some ART and renal impairment as we all know. Implications from one of the studies in this oral presentation indicate cumulative increasing risk of Chronic Kidney Disease with increasing exposure to TDF, ATV/r, LPV/r in persons with an initially normal eGFR. The risk is cumulative over time.

A reminder that individual's risk of CKD can be calculated using the D:A:D CKD risk score to help determine benefits/risk in incorporating ARVs into ongoing treatment regimen

and finally

6. Looking at Tenofovir Alafenamide (TAF)- the novel prodrug of Tenofovir (TDF) - we await in anticipation in Australia!!!!

2 large RCT with detailed protocol specified renal and bone end points, confirmed favourable safety and tolerability profile of TAF and that compared with TDF. TAF demonstrated no discontinuations due to renal Adverse effete, significantly smaller decreases in eGFR, significantly less proteinura, albuniuria and tubular proteinura, significanly less impact on spine and hip BMD and overall, greater increases in fasting lipids TC HDL same.

·Although there have been studies in the past demonstrating cART being associated with diabetes, hypertension, lipid problems, increased platelet activity etc. and various studies associating cART with myocardial infarction, Steven emphasized the importance of looking at the the newer studies showing the positive effect of cART with respect to cardiovascular risk.

·The SMART study and the potential mechanisms for beneficial effects of viral suppression on cardiovascular diseases including decreased I 6 and increased HDL.

Following on from a symposium on "Current Issues in HIV -related Malignancies" yesterday (webcasts now available) during which HIV associated malignancies were described as a worldwide epidemic, viral oncogenesis was discussed and a very rapid, high powered presentation on the advances and existing challenges of AIDS lymphoma to be followed immediately by the very humbling presentation on HIV malignancies in low and middle - income countries, it was of great interest to me to attend the themed discussion session on " Cancers in Young and Old and Lung Cancers in HIV"

It was useful to be reminded of the AIDS defining Cancers - Kaposi's Sarcoma, Non Hodgkin's Lymphoma and Cervical cancer and their associated etiological agents as well as the non AIDS defining cancers seen in HIV positive patients including Hodgkins Lymphoma, Anal, Lung and Liver carcinomas with their associated etiological agents.

In the US the most common AIDS defining cancer is Non- Hodgkin's Lymphoma. There have been recent decreases in Non AIDS defining cancers like Lung Ca and Hodgkin's Lymphoma but increases in liver and anal cancers. There was mention of prostate, breast and colorectal cancers although not in excess in HIV patients and with a greater association with ageing. Aging in the HIV population needs to be considered.

High Frequency of Early Lung Cancer Diagnosis with Chest CT in HIV -Infected Smokers

CD4 Measures as Predictors of Lung Cancer Risk and Prognosis in HIV infection

Key points summarised from these studies

ART was found to reduce the risk of developing cancer in HIV infected children in South Africa and the early link to care as well as the early start of ART is emphasised to further reduce the burden of cancer in these children

Elderly patients with HIV may have a higher risk for many cancers identified as HIV-associated in younger populations. The elevation of Non-Hodgkin's Lymphoma incidence in this population was notably lower in one of the studies possibly reflecting the high frequency of NHL subtypes less strongly associated with HIV in elderly adults. The increased risk associated with ageing and HIV together, in elderly patients infected with HIV, shows a sizeable absolute risk of cancer. The need for cancer prevention and screening in this population was emphasised.

Smoking cessation programs were emphasised amongst adolescents and young adults at risk for HIVV with suggestions that this could prevent up to 46% of non AIDS defining Cancers in HIV infected adults. This emphasises the importance of primary care involvement in this population. Using ART to preserve immune status, maintain HIV viral suppression and preventing AIDs defining illnesses could prevent only up to 6% of non AIDS Defining Cancers in HIV infected adults. So, effective interventions to reduce smoking were emphasised with a continued HIV treatment focus.

Interestingly , one study showed that early lung cancer diagnosis and nodule followup with chest CT was feasible in HIV infected smokers with detection of surgically curable cancers. This study raised a lot of discussion on screening for lung cancer. I would recommend you look at the webcast when available

Finally another study found several measures of recent and cumulative exposure in immunodeficiency associated with increased risk lung cancer.

Continued vigilance of the issue of malignancy in primary care and specialist care of HIV patients needs to be emphasised.

The use of hormonal contraceptives in HIV medicine has been clouded with controversy. Do hormonal contraceptives increase HIV risk and influence a woman's susceptibility to HIV infection? From a sexual health point of view, this has been of interest to me.

This themed discussion was led by Betsy Harold from the Albert Einstein College of Medicine at the Bronx, New York and is available now on the CROI webcast. She introduced the session by pointing out that a recent meta-analysis of 18 studies including 37,124 women and 1830 HIV incident infections concluded an adjusted hazard ratio relative to no hormonal contraceptives for DMPA to be 1.50 (1.25-1.83) and for COC to be 1.03 (0.8-1.2). HIV infections appear to be be seen more often in women on DMPA and COC. She mentioned the biological plausibility of these findings including thinning epithelium, increased CCR5 expression, changes in micro biome, increased HSV and other STIs, ulcerative lesions and increased pro-inflammatory or decreased protective mediators.

It is thought that hormonal contraception may increase CCR5 expression favouring HIV infectivity and that oestrogen may modulate CCR5 expression

In this study, there is a suggestion that there could be an increased risk of HIV acquisition in older postmenopausal women in that CCR5 is elevated, especially in cervical CD4+cells compared to premenopausal women. Oestrogen replacement was found to reduce %CCR5+CD4+ T cells in these postmenopausal women suggesting it could decrease HIV acquisition in this group. It is noted though that the population studied was healthy.

This study suggested that the use of LNG-IUD and DMPA was associated with increased CCR5 expression on peripheral T cells and that comparative work in the female reproductive tract tissues and blood is needed to evaluate further increases in CCR5 expression associated with hormonal contraception. Again, the study was on uninfected women.

Progesterone Increases are Associated with HIV Susceptibility Factors in Women

Native progesterone and progestin based hormonal contraception are suspected of HIV acquisition risk in women although how these contraceptives affect HIV target cells is uncertain. The results of this study appear to suggest that the endogenous progesterone increase during the menstrual cycle luteal phase is associated with HIV target cells that have increased CCR5 expression, higher levels of activation and response to stimulation. If these progesterone effects exist in genital mucosa, this could be an important measure for identifying progestin based hormonal contraceptive risk factors.

This study looked at the changes in vaginal microbiota and inflammatory milieu after DMPA initiation through which it is thought DMPA may modify HIV susceptibility. The initiation of DMPA was shown to demonstrate sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators after adjusting for behavioural and biological confounders possibly impacting on HIV susceptibility. I am reminded of the association between bacterial vaginosis and HIV transmission.

As was pointed out by Betsy Harold, studies in this area have been retrospective studies and there is a need for prospective studies to occur

The oral presentations during this session were excellent and should be available very soon.

They included the Proud Study from the UK, On-demand PrEP with oral TDC-FTC in MSM - results of the ANRS Ipergay Trial, The Demonstration Project of PrEP and ART, Scale-up Pre-exposure Prophylaxis in San Francisco to impact HIV incidence, the FACTS 001 Phase 3 Trial of Pericoital Tenoforvir 1% gel for HIV Prevention in Women, the Effect of oral and gel Tenofovir on Genital HSV Shedding in immunocompetent Women, Injectable Hormonal Contraception Use and Women's Risk for HSV 2 Acquisition, Medical Male Circumcision of HIV -Infected Men reducing long term penile HIV shedding.

There are some exciting results from these studies which may impact what is happening in Australia.

From a sexual health point of view, I note with interest the study where consistent DMPA use may increase women's risk of HSV2 acquisition. Obviously as pointed out, evaluation in larger populations with more frequent follow up is needed. It was also important that they pointed out that the issue of increased HIV and HSV-2 associated with DMPA needed to be weighed against benefits, reduced risk maternal mortality and unwanted pregnancy.

I intend to report back more on the session on Hormonal Contraception and HIV in Women.

It was also very useful to revisit yet again the issue of medical male circumcision where the study concerned noted penile shedding of HIV increasing at 1-2 weeks after medical circumcision in ART naive men but then, penile HIV shedding became significantly lower after wound healing later. They concluded that suppressive ART decreased number of HIV shedding events and quantity of HIV shedding during would healing. There was re-enforcemnt of the long term benefits of MC in HIV positive men reducing penile HIV shedding. However the importance of prevention of HIV transmission to partners during immediate post surgical period was emphasised. Initiating ART at time of MC reduced male to female HIV transmission risk. Implications in Australia???